A randomized diet-induced weight-loss intervention reduces plasma complement C3: Possible implication for endothelial
Shunxin Jin1, Yvo H A M Kusters1,2, Alfons J H M Houben1
1Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University and Medical Center, Maastricht, The Netherlands.
Insights
Weight loss interventions can reduce complement C3 levels in men with obesity, potentially improving cardiovascular health by reducing endothelial dysfunction. This highlights a key mechanism linking weight management to reduced cardiovascular disease risk.
Area of Science:
- Cardiovascular Science
- Metabolic Research
- Immunology
Background:
- Elevated complement C3 and alternative pathway components are linked to obesity.
- Complement C3 is a recognized risk factor for cardiovascular disease.
- Understanding C3 regulation in obesity is crucial for cardiovascular risk mitigation.
Purpose of the Study:
- To investigate the impact of a weight-loss intervention on plasma C3, C3a, and factor D levels.
- To explore the biological effects of reduced C3 following weight loss.
- To determine the relationship between C3 reduction and improvements in endothelial dysfunction markers.
Main Methods:
- Plasma C3, C3a, and factor D were quantified using ELISA.
- Visceral adipose tissue, subcutaneous adipose tissue, and intrahepatic lipid were assessed via MRI.
- Men with obesity underwent an 8-week dietary weight-loss intervention or maintained their habitual diet.
Main Results:
- The weight-loss intervention significantly reduced plasma C3 levels.
- C3 reduction was primarily associated with decreased visceral adipose tissue, not subcutaneous adipose tissue or intrahepatic lipid.
- Reduced C3 partially explained improvements in endothelial dysfunction markers, including soluble endothelial selectin and intercellular adhesion molecule.
Conclusions:
- Diet-induced weight loss in men with abdominal obesity effectively lowers plasma C3.
- C3 reduction may mediate the beneficial effects of weight loss on endothelial function.
- Lowering C3 through weight management could be a strategy to ameliorate cardiovascular disease risk in obese individuals.
Objective:
Complement C3 and other components of the alternative pathway are higher in individuals with obesity. Moreover, C3 has been identified as a risk factor for cardiovascular disease. This study investigated whether, and how, a weight-loss intervention reduced plasma C3, activated C3 (C3a), and factor D and explored potential biological effects of such a reduction.
Methods:
The study measured plasma C3, C3a, and factor D by ELISA and measured visceral adipose tissue, subcutaneous adipose tissue, and intrahepatic lipid by magnetic resonance imaging in lean men (n = 25) and men with abdominal obesity (n = 52). The men with obesity were randomized to habitual diet or an 8-week dietary weight-loss intervention.
Results:
The intervention significantly reduced C3 (-0.15 g/L [95% CI: -0.23 to -0.07]), but not C3a or factor D. The C3 reduction was mainly explained by reduction in visceral adipose tissue but not subcutaneous adipose tissue or intrahepatic lipid. This reduction in C3 explained a part of the weight-loss-induced improvement of markers of endothelial dysfunction, particularly the reduction in soluble endothelial selectin and soluble intercellular adhesion molecule.
Conclusions:
Diet-induced weight loss in men with abdominal obesity could be a way to lower plasma C3 and thereby improve endothelial dysfunction. C3 reduction may be part of the mechanism via which diet-induced weight loss could ameliorate the risk of cardiovascular disease in men with abdominal obesity.
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